PDBsum entry 3ctr

Hydrolase

PDB id: 3ctr

Contents

Protein chain

75 a.a. *

Ligands

MGP

Waters ×69

* Residue conservation analysis

PDB id:

3ctr

Name:

Hydrolase

Title:

Crystal structure of the rrm-domain of the poly(a)-specific ribonuclease parn bound to m7gtp

Structure:

Poly(a)-specific ribonuclease parn. Chain: a. Fragment: RNA-recognition-motif of parn (residues 445-540). Synonym: polyadenylate-specific ribonuclease, deadenylating nuclease, deadenylation nuclease. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: parn, dan. Expressed in: escherichia coli.

Resolution:

2.10Å R-factor: 0.211 R-free: 0.243

Authors:

T.Monecke,S.Schell,A.Dickmanns,R.Ficner

Key ref:

T.Monecke et al. (2008). Crystal structure of the RRM domain of poly(A)-specific ribonuclease reveals a novel m(7)G-cap-binding mode. J Mol Biol, 382, 827-834. PubMed id: 18694759 DOI: 10.1016/j.jmb.2008.07.073

Date:

14-Apr-08 Release date: 29-Jul-08

Protein chain

O95453  (PARN_HUMAN) -  Poly(A)-specific ribonuclease PARN from Homo sapiens

Seq: 639 a.a.

Struc: 75 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.13.4 - poly(A)-specific ribonuclease.
• Reaction: Exonucleolytic cleavage of poly(A) to 5'-AMP.

DOI no: 10.1016/j.jmb.2008.07.073

J Mol Biol 382:827-834 (2008)

PubMed id: 18694759

Crystal structure of the RRM domain of poly(A)-specific ribonuclease reveals a novel m(7)G-cap-binding mode.

T.Monecke, S.Schell, A.Dickmanns, R.Ficner.

ABSTRACT

Poly(A)-specific ribonuclease (PARN) is a processive 3'-exoribonuclease involved in the decay of eukaryotic mRNAs. Interestingly, PARN interacts not only with the 3' end of the mRNA but also with its 5' end as PARN contains an RRM domain that specifically binds both the poly(A) tail and the 7-methylguanosine (m(7)G) cap. The interaction of PARN with the 5' cap of mRNAs stimulates the deadenylation activity and enhances the processivity of this reaction. We have determined the crystal structure of the PARN-RRM domain with a bound m(7)G triphosphate nucleotide, revealing a novel binding mode for the m(7)G cap. The structure of the m(7)G binding pocket is located outside of the canonical RNA-binding surface of the RRM domain and differs significantly from that of other m(7)G-cap-binding proteins. The crystal structure also shows a remarkable conformational flexibility of the RRM domain, leading to a perfect exchange of two alpha-helices with an adjacent protein molecule in the crystal lattice.

Selected figure(s)

Figure 2.
Fig. 2. The crystallographic dimer mimics the NMR structure. The protruding C-terminal α2 and α3 helices of each monomer pack on the N-terminal β-sheet in a way that they mimic the NMR structure (colored gray) of the PARN-RRM (PDB code: 1WHV). The loop between the α2 and α3 helices corresponds to the fourth β-strand of the canonical RRM fold.

Figure 3.
Fig. 3. Detailed view of the cap binding site of the PARN-RRM with bound m^7GTP. The m^7GTP cap (shown in ball-and-stick mode) binds on the surface of the N-terminal part of the RRM domain involving the loops connecting β2 and β3 strands as well as the β1 strand and the α1 helix. The 2|F[o]| − |F[c]| electron density (blue) corresponding to the bound m^7GTP is contoured at 1.1 σ. The interacting residues are depicted in ball-and-stick mode. The guanine moiety stacks on the side chain of Trp475 and is bound by several hydrogen bonds. A water molecule mediating hydrogen bonds between Thr458 and the exocyclic oxygen O6 of the cap guanine is colored orange.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 382, 827-834) copyright 2008.

Figures were selected by an automated process.